期刊
JOURNAL OF CONTROLLED RELEASE
卷 322, 期 -, 页码 170-176出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.03.019
关键词
Pulmonary systemic drug delivery; Zwitterionic polymer; Bioscavenger; Pharmacokinetics; Bioavailability
资金
- Defense Threat Reduction Agency [HDTRA1-13-1-0044]
- University of Washington
Pulmonary delivery of protein drugs into the systemic circulation is highly desirable as the lung provides a large absorption surface area and a more favorable environment for biologics compared to other delivery routes. However, pulmonary systemic delivery of proteins presents several challenges such as poor protein stability and limited bioavailability, especially for large proteins (molecular weight > 50 kDa), which exhibit an average bioavailability of 1% to 5% when delivered via the pulmonary route. Here, we demonstrated that with the conjugation of zwitterionic poly(carboxybetaine) (pCB) polymer, the bioavailability of organophosphate hydrolase (OPH) was significantly increased from 5% to 53%. OPH conjugated with pCB delivered through intubation-assisted intratracheal instillation (IAIS) into the lung exhibited improved pharmacokinetic properties and prophylactic efficacy against organophosphate poisoning, showing its application potential. Zwitterionic polymer conjugation provides the possibility for a favorable, non-invasive delivery of biological therapeutics into the systemic circulation.
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